Linking Probabilistic Exposure and Pharmacokinetic Modeling To Assess the Cumulative Risk from the Bisphenols BPA, BPS, BPF, and BPAF for Europeans

The bisphenols S, F, and AF (BPS, BPF, and BPAF) are used to replace the endocrine disrupting chemical bisphenol A (BPA) while exerting estrogenic effects of comparable potency. We assessed the cumulative risk for the aforementioned BPs in Europe and compared the risk before and after the year 2011, which was when the first BPA restrictions became effective. For this, we probabilistically modeled external exposures from food, personal care products (PCPs), thermal paper, and dust (using the tools MCRA and PACEM for exposures from food and PCPs, respectively). We calculated internal concentrations of unconjugated BPs with substance-specific PBPK models and cumulated these concentrations normalized by estrogenic potency. The resulting mean internal cumulative exposures to unconjugated BPs were 3.8 and 2.1 ng/kg bw/day before and after restrictions, respectively. This decline was mainly caused by the replacement of BPA by BPS in thermal paper and the lower dermal uptake of BPS compared to BPA. However, the decline was not significant: the selected uncertainty intervals overlapped (P2.5-P97.5 uncertainty intervals of 2.7-4.9 and 1.3-6.3 ng/kg bw/day before and after restrictions, respectively). The upper uncertainty bounds for cumulative exposure were higher after restrictions, which reflects the larger uncertainty around exposures to substitutes compared to BPA.